Very late antigens VLA-1, VLA-2, VLA-3, and VLA-6, belonging to the beta 1 subfamily of integrins, have been identified as receptors for different binding domains of laminin (LM). We have detected VLA-6, but not VLA-1 and VLA-2 on a subset (50-70%) of fresh peripheral blood CD3- , CD16+, CD56+ human natural killer (NK) cells by immunofluorimetric and biochemical analysis. Binding assays performed on LM-coated plates showed that 10-15% of NK cells spontaneously adhere to LM, and this adhesion is mediated by VLA-6. Activation of NK cells through CD16 triggering or by phorbol ester results in a rapid increase of adhesion to LM, which is still mediated by VLA-6. The enhanced adhesiveness is not associated with changes in beta 1 LM receptor expression, while it correlates with changes in the phosphorylation status of alpha 6 subunit. The expression of VLA-6 on NK cells and the modulation of its avidity by activating stimuli may be relevant for NK cell migration and tissue location during inflammation or immune response.


We develop a theory for scaling properties of quantum transport in nano-field effect transistors. Our starting point is a one-dimensional effective expression for the drain current in the Landauer-Büttiker formalism. Assuming a relatively simple total potential acting on the electrons the effective theory can be reduced to a scale-invariant form yielding a set of dimensionless control parameters. Among these control parameters are the characteristic length l and -width w of the electron channel which are its physical length and -width in units of the scaling length . Here is the Fermi energy in the source contact and is the effective mass in the electron channel. In the limit of wide transistors and low temperatures we evaluate the scale-invariant i-v characteristics as a function of the characteristic length. In the strong barrier regime, i. e. for long-channel behavior is found. At weaker barriers source-drain tunneling leads to increasingly significant deviations from the long-channel behavior.


This paper focuses on the decomposition of real wages in Colombia both by workers' ages and by cohorts, which overlap over time. The paper analyses how the Colombia's labour structure has undergone important changes in the period 1982-2007. This period has been characterized by a demographic transition that has tilted the balance from a relatively young population to an older one. The effects of capital accumulation have been estimated and modelled considering the presence of ever more sophisticated machinery, usually replacing less-skilled, younger workers, in relation to older and more qualified ones. In general real wages present a curved shape for each generation, as is acknowledged in the life-cycle hypothesis, according to which people generally start their working life with low incomes and rising debts and then obtain higher income and accumulate assets.


Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for an array of problematic community- and healthcare-acquired infections, including pneumonia, and is frequently associated with severe disease and high mortality rates. Standard recommended treatments for empiric and targeted coverage of suspected MRSA in patients with community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP), are vancomycin and linezolid. However, adverse events such as acute kidney injury and Clostridium difficile infection have been associated with these antibiotics. Ceftaroline fosamil is a β-lactam/extended-spectrum cephalosporin approved for the treatment of adults and children with CAP and complicated skin and soft tissue infections. Ceftaroline has in vitro activity against a range of common Gram-positive bacteria and is distinct among the β-lactams in retaining activity against MRSA. Due to the design of the pivotal randomised controlled trials of ceftaroline fosamil, outcomes in patients with MRSA CAP were not evaluated. However, various reports of real-world outcomes with ceftaroline fosamil for pneumonia caused by MRSA, including CAP and HAP/VAP, been published since its approval. A systematic literature review and qualitative analysis of relevant publications was undertaken to collate and summarise relevant published data on the efficacy and safety of ceftaroline fosamil in patients with MRSA pneumonia. While relatively few real-world outcomes studies are available, the available data suggest that ceftaroline fosamil is a possible alternative to linezolid and vancomycin for MRSA pneumonia. Specific scenarios in which ceftaroline fosamil might be considered include bacteraemia and complicating factors such as empyema.


We present a technique for accurate wideband measurements of one-port devices with extreme impedances. Our technique uses a reflectometer with variable parameters (states) to obtain redundant measurements of the extreme impedance device. We process these measurements using statistical techniques that allow us to exploit the redundancy in order to increase the measurement bandwidth and reduce the measurement uncertainty. We demonstrate our technique for a simple setup containing a power splitter and an unknown variable reference impedance connected to one of its arms and an unknown extreme-impedance device connected to its other arm. The variable reference impedance is realized as either a set of mechanical standards or an electronically tunable impedance. Measurement results show that the repeatability of the reference impedance values is essential for achieving increased accuracy.


Archean basement rocks occur in the core of a fold nappe in the northern East Humboldt Range, Nevada. The Archean rocks consist primarily of plutonic orthogneiss and metasedimentary paragneiss. Both units contain numerous amphibolitic bodies interpreted as mafic intrusions. U-Pb zircon studies indicate that the orthogneiss unit is at least 2520 ±110 Ma and therefore is an example of an Archean granitoid. These data extend the known distribution of Precambrian basement rocks into northeastern Nevada and provide new constraints on the delineation of the Archean Wyoming province. The basement rocks are surrounded by upper amphibolite facies, metasedimentary rocks correlated with late Precambrian to Devonian(?) rocks of the eastern Great Basin miogeoclinal sequence. The contact between the Archean basement rocks and the metasedimentary mio geoclinal sequence is interpreted as a premetamorphic and prefolding, low-angle fault. The age and prefolding geometry of this low-angle fault are currently poorly constrained, but it may record important Mesozoic crustal shortening in the hinterland of the Sevier orogenic belt. The age of nappe formation is not yet fully established, but at least some isoclinal folds in the area were formed in the Tertiary and are kinematically linked to a major extensional deformation.


Platinum agents and paclitaxel (taxol) are among the most effective drugs currently available for treatment of ovarian cancer. One of the hurdles with taxol and platinum- based therapy is the clinical development of resistance to these agents. To investigate the mechanism of drug resistance in human ovarian cancer, we developed and characterized 5 cell models for chemoresistance studies of cisplatin, carboplatin and taxol. We report in this study that these human ovarian carcinoma cell model systems include 2 models for cisplatin resistance, 2 models for carboplatin resistance, and 1 model for taxol resistance. The biological and biochemical characteristics of the models showed that (i), the IC50 values of the drugs for all these resistant cell models were 3 times (or more) higher than those for the parental tumor cells. There also exist varying degrees of cross-resistance to several other chemotherapeutic agents in these systems. Moreover, the intracellular drug accumulations in these cells were significantly reduced as compared to those in the parental cells. (ii), The proliferation rates of these resistant cells were markedly decreased. However, there were no obvious changes in cell cycle distribution in these model systems. (iii), Our results for the expression of a few major drug resistance-related genes revealed that the expression of p53, lrp-1 and mrp-1 was decreased, while the expression of pkc, topo I and topo II beta was increased in the resistant tumor cells as compared with the parental cells. In contrast, no significant alterations in gst-pi and topo II alpha expression were found. Interestingly, the levels of mdr-1 expression were elevated in some models, but were reduced in others, thus suggesting that different pathways are involved in the formation of drug resistance in different cell model systems, and that different mechanisms are responsible for the development of different drug resistances in tumor cells. Taken together, our findings indicate that these models may be potentially used to assess the biochemical and genetic mechanisms of drug resistance in human ovarian cancer and to identify new drug resistance-related genes.


Drawing on surveys of 4,860 prisoners' perceptions of the quality of prison life in 49 establishments in England and Wales, this paper examines the extent to which prisoners viewed race relations in prison as problematic. Emphasis was placed upon how aspects of race relations were rated by different ethnic groups, and in individual prisons. Significant differences were found between prisons of the same security category. The findings support those of previous studies in that they raise concerns about the treatment of ethnic minority prisoners, particularly in some prisons. Attention was also paid to the role of gender, age and the security category of the prison. Ethnic minority prisoners tended to rate the quality of race relations in prison more poorly than their White counterparts. Large proportions amongst all ethnic minority groups felt that they were subject to unfair treatment compared to the White majority. On the whole, female prisoners were more likely than males to rate the quality of race relations more favourably, as were adult prisoners in comparison to their young counterparts. Gender and age had a considerable impact on the views of ethnic minority prisoners on the quality of race relations in the establishment. Perceived quality of race relations was significantly associated with prisoners' views on more general aspects of their treatment in prison, such as respect, humanity, fairness, relationships with staff and safety. Neither the ethnic composition of each prison's population nor the respective ratio of White to ethnic minority staff had a significant impact on how prisoners viewed the quality of race relations. These results suggest, amongst other things, that perceptions of the legitimacy of penal practices differ significantly between age and ethnic groups, and that attempts to reduce discrimination work more effectively in relation to distributive practices than in relation to attitudes and general treatment.


The enteric nervous system (ENS), a collection of neurons contained in the wall of the gut, is of fundamental importance to gastrointestinal and systemic health. According to the prevailing paradigm, the ENS arises from progenitor cells migrating from the embryonic neural crest and remains largely unchanged thereafter. Here, we show that the composition of maturing ENS changes with time, with a decline in neural-crest derived neurons and their replacement by mesoderm-derived neurons. Single cell transcriptomics and immunochemical approaches establish a distinct expression profile of mesoderm-derived neurons. The dynamic balance between the proportions of neurons from these two different lineages in the post-natal gut is dependent on the availability of their respective trophic signals, GDNF-RET and HGF-MET. With increasing age, the mesoderm-derived neurons become the dominant form of neurons in the ENS, a change associated with significant functional effects on intestinal motility. Normal intestinal function in the adult gastrointestinal tract therefore appears to require an optimal balance between these two distinct lineages within the ENS.


Oxygen ion migration is an important factor in the formation and rupture of a conducting filament to cause resistive switching (RS) behavior. A calcium oxide-doped zirconium oxide (CaO:ZrO2) oxygen ion conductor buffer layer is introduced between the Ti/ZrO2 interface of conventional Ti/ZrO2/Pt memory devices to improve their unipolar RS properties. Increasing the CaO doping concentration to 2 mol% introduces higher oxygen vacancy content within the CaO:ZrO2 buffer layer, leading to higher oxygen ion conductivity. This allows more oxygen ions to migrate from the oxygen reservoir laterally and vertically across the 2-mol% CaO:ZrO2 buffer layer to the region where the conducting filament forms and ruptures. Therefore, the Ti/2-mol% CaO:ZrO2/ZrO2/Pt device in this letter exhibits good endurance, high-speed switching (50 ns) without soft errors, stubborn nondestructive readout, and stable retention at 150°C.


Three actinomycetous strains designated as LIA-0773, LIA-0783 and LIA-0780 were isolated from various soil samples. The cultures actively inhibited the growth of Trichophyton gipseum and produced a non-polyenic antibiotic of the chondamycin type. The strains were identified with Act. griseochromogenes Fukunaga et. al., 1955. The cultures differed within the species by some morphological, cultural, physiological and antibiotic properties, as well as by the component composition of the antibiotic produced. Thus, strain LIA-0773 had larger spiral sporophores, satisfactorily hydrolized starch and inverted sucrose. The strain inhibited the growth of not only the fungi but also grampositive bacteria and mycobacteria and produced an antibiotic composed of 6 components. Strain LIA-0780 had small sporophores with close spirals and low amilolytic activity. It inhibited only the growth of the fungi and produced a monocomponent antibiotic. Strain LIA-0783 was intermediate. By its biological properties it was closer to strain LIA-0780. The antibiotic produced by it consisted of 6 components, while by its physico-chemical properties the antibiotic was close to that produced by strain LIA-0780. All the 3 actinomycetous cultures were considered as different variants of Act. griseochromogenes Fukunaga et al., 1955.


Diminishing yields for modern CMOS and emerging technologies have become a major growing concern for IC manufacturers due to its direct impact on revenue. To this end, "Design for Yield (DFY)" have been proposed to proactively address manufacturing yield issues in the system design stage. While many DFY approaches have been developed for caches, GPUs and CPUs, they remain decoupled from each other, which is not ideal for modern microprocessors or MPSoCs that integrate multiple components onto a single die. In this paper we introduce "Global Yield and Floorplan Aware Design Optimization Framework (GlYFF)", a holistic computer-aided DFY framework that unifies redundancy based yield-centric design optimizations and floorplanning for MP-SoCs. GlYFF recognizes the different yield enhancement strategies for different on-die components, and is able to output detailed floorplans for accurate area/performance measurements. We demonstrate that compared to a segregated DFY methodology, GlYFF can achieve ~20% improvement in yield-per-area, a metric strongly correlated to revenue.


Electrical stimulation of nerves to isolated rat and rabbit adipose tissue in vitro causes production of free fatty acids. Starvation increases the response. The response of white (epididymal) fat is prevented by sympathetic denervation. Direct evidence is provided showing that adipose tissue has the capacity to be an effector organ responsive to the nervous system.


Field experiments were conducted with Cucurbita pepo L. 'Howden∑ pumpkin in 2000 to 2001 to study the effects of silicon (Si) amendment of soil with and without the use of fungicides on yield and powdery mildew suppression. A Quakertown silt loam soil (fine-loamy, mixed, mesic Typic Hapludult) with an initial soil pH of 5.7 was amended with either CaCO 3 or CaSiO3 at the rate of 7840 kg·ha -1 of calcium carbonate equivalent. Fungicides were applied on a 7-10 day schedule to half of the plots as a 2 × 2 factorial, begin- ning when the first powdery mildew lesions were detected in the field. Silicon amendment increased pumpkin yield by 60% in 2000 but Si did not influence yield in 2001. Infection with bacterial leaf spot reduced yield on all plots in 2001. Fungicide applications increased yield only in 2001. In 2000, Si amendment had the effect of delaying foliage senescence but it was not clear if this was the result of an effect of Si on disease activity or crop physiology. In Aug. 2001, Si amendment generally reduced powdery mildew severity, but only at the 10% level of significance. In Sept. 2001, the combination of Si amendment plus fungicide application was more effective in reducing powdery mildew severity than either Si or fungicide alone. Silicon amendment resulted in a 5-fold increase in plant Si concentration. Soil pH measured after harvest in 2001 indicated no significant difference in pH between plots amended with CaCO 3 (pH = 6.8) and CaSiO3 (pH = 6.9). In New Jersey, the cost of these liming materials is similar. Thus, the selection of CaSiO 3 as a liming material as needed for soil pH correction has the potential benefits of suppressing powdery mildew and increasing pumpkin yield without increasing the cost of production.


The U-Net was presented in 2015. With its straight-forward and successful architecture it quickly evolved to a commonly used benchmark in medical image segmentation. The adaptation of the U-Net to novel problems, however, comprises several degrees of freedom regarding the exact architecture, preprocessing, training and inference. These choices are not independent of each other and substantially impact the overall performance. The present paper introduces the nnU-Net ('no-new-Net'), which refers to a robust and self-adapting framework on the basis of 2D and 3D vanilla U-Nets. We argue the strong case for taking away superfluous bells and whistles of many proposed network designs and instead focus on the remaining aspects that make out the performance and generalizability of a method. We evaluate the nnU-Net in the context of the Medical Segmentation Decathlon challenge, which measures segmentation performance in ten disciplines comprising distinct entities, image modalities, image geometries and dataset sizes, with no manual adjustments between datasets allowed. At the time of manuscript submission, nnU-Net achieves the highest mean dice scores across all classes and seven phase 1 tasks (except class 1 in BrainTumour) in the online leaderboard of the challenge.


High Efficiency Video Coding (HEVC) is the latest video compression standard finalized
in year 2013. While H.264/Advance Video Coding (AVC) is still the mostly
deployed video-coding standard, HEVC is gaining ground, especially for storage and
transmission of high-resolution videos such as High Definition (HD), 4K, 8K and beyond.
In this thesis, video authentication based on information hiding technique is studied.
The concept of authentication, layout and implementation are presented under the
latest HEVC video compression standard. One of the unique properties of HEVC standard,
i.e., combination of coding unit size, which is sensitive to video manipulation, is
utilized in the proposed information hiding technique. A video authentication scheme is
then put forward by exploiting this unique property of HEVC to embed authentication
code based on a predefined mapping rule. In addition, temporal dependency is enforced,
where the authentication tag generated in one video slice is embedded into its subsequent
slice. Furthermore, multiple layers of authentication are presented to detect and localize
the tampered regions in a HEVC video, as well as verifying the source / sender of the
video using a shared secret key. Moreover, several encryption techniques are presented
to incorporate with the proposed scheme to achieve video authentication in encrypted
domain without compromising on compression efficiency. Video sequences from various
classes (i.e., resolutions) are considered to verify the performance of the proposed
multi-layer authentication scheme. Results show that, at the expense of slight degradation
in perceptual quality, the proposed scheme is robust against video tampering within and
across video slices. Lastly, a functional comparison is performed between the proposed
authentication scheme and the conventional schemes for both plaintext and ciphertext
(encrypted) videos.


Background
Adaptive radiation therapy (ART) is moving into the clinic rapidly. Capability of delineating the tumor change as a result of treatment response during treatment delivery is essential for ART. During image-guided radiation therapy (IGRT), a CT or cone-beam CT is taken at the time of daily setup and the tumor is not visible by eye in regions of soft tissue due to low contrast. The scope of this paper is to develop a method using a classifier trained on non-contrast CT textures, to estimate the gross tumor volume (GTV) of the day (GTVd) from daily (longitudinal) CTs acquired during the course of IGRT when the tumor is not visible.

Methods
CT textures from daily diagnostic-quality CTs routinely acquired during IGRT using an in-room CT were analyzed. Pretreatment GTV was delineated from pre-RT diagnostic images and populated to the first daily CT. Maps of first-order textures (mean, SD, entropy, skewness and kurtosis) and short-range second-order textures were created from the first daily CT. The classifier was trained to sort voxels into GTV and surrounding tissue on subsequent daily CTs over the course of RT. Optimum combinations of textures was defined by repeating the training process with all possible texture combinations. The trained classifier was used to identify voxels belonging to the GTVd, based on the CT of the day. Posttreatment GTV delineated from the post-RT follow-up images was populated to the last daily CT and used to validate the last GTVd delineated by the classifier. To demonstrate the concept, the method was described using three representative treatment sites, e.g., lung, breast and pancreatic tumors.

Results
Comparing the classifier map generated from a new CT to the initial training CT, the dice coefficient (DC) for GTV in lung is 83% on the eighth treatment and 84% on the last. The DC for the breast GTV is 56% mid-treatment and 65% at the last treatment. In the case of the pancreas with the least in organ tissue contrast, the DC for 4 cases ranges from 21% to 77% for the last treatment compared with the post-RT diagnostic CT. The Housdorff distance (HD) ranged from 2.9 to 5.9 mm with the mean GTV RECIST dimension of 22.75 mm long by 14.7 mm short.

Conclusions
It is feasible to estimate the general region of the GTV of the day from the daily CT acquired during RT, based on CT textures, using a trained voxel classifier algorithm. The obtained GTV may be used as a starting point for an accurate GTV delineation in online adaptive replanning. Further study with larger patient datasets is required to improve the robustness of the algorithms.


Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the source is credited. DOI 10.3109/17453674.2012.747925 Background and purpose Historically, the treatment of periprosthetic femoral fractures (PFFs) has been associated with a high frequency of complications and reoperations. The preferred treatment is internal fixation, a revision of the femoral stem, or a combination of both. An improved understanding of plate use during internal fixation, and the introduction of locking-plate osteosynthesis may lead to improved outcome. We evaluated the outcome of Vancouver type B1 and C PFFs treated by lockingplate osteosynthesis, by assessing rates of fracture union and reoperations and by analyzing failure cases. Patients and methods From 2002 through 2011, 58 consecutive patients (60 fractures) with low-energy PFF around or below a stable femoral stem, i.e. Vancouver type B1 and C fractures, underwent osteosynthesis with a locking plate. All patients had a total hip replacement (THR). They were followed up clinically and radiographically, with 6 weeks between visits, until fracture union or until death. Fracture union was evaluated 6 months postoperatively. Results At a median follow-up time of 23 (0–121) months after PFF, 8 patients (8 fractures) had been reoperated due either to infection (n = 4), failure of fixation (n = 3), or loosening of the femoral stem (n = 1). All the patients who had been followed up for at least 6 months—and who did not undergo reoperation or die—went on to fracture union (n = 43). Interpretation Locking-plate osteosynthesis of periprosthetic Vancouver type B1 and C fractures gives good results regarding fracture union. It appears that spanning of the prosthesis to avoid stress-rising areas is important for successful treatment. Infection is the major cause of failure.


The author seeks to destroy the myth surrounding the personality of Mikhail Katkov, one of Russia's most prominent thinkers and journalists, who defended the Russian imperial ideology, believing it to have descended from European views to take root in the local culture. The author invokes two major figures of Russian history and culture: Peter the Great and the poet Aleksandr Pushkin. Katkov argued that Russia owed its successful integration into European history to Peter the Great, who transformed the country into a powerful empire and created an independent space for spiritual experiments. So it no longer seems accidental that Pushkin was referred to as 'the singer of the empire and freedom'. It was for that reason that Katkov jumps to the defence of the Russian empire, fearlessly opposing the government, no less, who, he thought, had lost touch with reality. Eventually, Katkov was fighting two enemies: Russian nihilists (with Herzen in the lead), who wasted no time undermining the empire, and Russian liberals, who would stop at nothing, even welcome a foreign invasion, in order to bring down the empire (the so-called 'Polish intrigue'). The author sets out to reconstruct the writer's true image through his work.


BACKGROUND
The study presents the advantages of the psychiatric liaison-attachment scheme, by analyzing the psychiatric consultations of a 12 months period (1995), in an urban family medicine clinic in Israel.

METHOD
Family physicians filled a questionnaire about all patients who had been seen at the consultation.

RESULTS
The consulting psychiatrist saw 46 patients. The reasons for consultation were mostly to confirm a diagnosis and to decide upon medications. Medical diagnoses most often made were depression and personality disorder. The psychiatrist referred 35% of patients for further therapy in the psychiatric clinic. The family physicians would have referred 45% of patients to psychiatric clinics, if they had no psychiatric consultation available. All patients referred complied with the recommended referral. Family physicians saw accessibility as the main advantage of this consultation strategy.

LIMITATIONS
This study was done in a unique setting, a teaching family medicine clinic, with nine specialized family physicians working in the psychiatric liaison-attachment scheme for as long as 10 years and more. Therefore the results of this study may not be generalized to other clinics.

CONCLUSIONS
We conclude that the advantages of the psychiatric liaison-consultation method were for the patients, the family physicians and the psychiatric consultant. The main advantages for the family physicians, as stated by them, were the accessibility, the non-stigmatic availability of a psychiatrist in the clinic, and the good compliance with referral to psychiatric therapy. For the consulting psychiatrist, the advantages were the valuable information from the family physicians and the social worker, the better follow-up of patients and the team work with the family practice team.


Prostitution in Burmese society, as in many South East Asian countries, is a taboo subject. Unlike prostitution in countries such as Thailand, however, prostitution in Burma does not attract strong media or scholarly debate. The state and the media in Burma, during both colonial and post-colonial periods, have tended and tend to see the problem of prostitution as one of 'others'. Colonialism, a decline in morality and the corruption of women influenced by modernity or Western culture have often been portrayed as the culprits. This article analyses the Burmese terms for prostitutes and examines how prostitution was portrayed by the print media between 1942 and 1962, during which time the press was thought to have enjoyed a certain degree of freedom. Seen as a threat to the British troops during the colonial period, prostitutes were subject to controversial medical screenings; yet, seen as victims of modernity during Burma's parliamentary period (1948–62), they were often left on their own to 'resurrect' their morality.


This paper provides a comparative study, through simulation, of the effectiveness of the local (decoupled) PD control and the neural network control when applied to a new biped robot model. The biped model has 5_link and 6 degrees of freedom and actuated by Plated Pneumatic Artificial Muscle, which have a very high power to weight ratio and an inherent adaptable compliance. This NN controller allow accurate and dynamic following of prescribed trajectories, not simply control using "via" points specified by a teach pendant. It can significantly improve the accuracy requirements by retraining the basic PD/PID loop, but adding an inner adaptive loop that allows the controller to learn unknown parameters such as friction coefficient, thereby improving tracking accuracy. Simulation results show that NN controller tracking performance is much better than PD controller tracking performance.


OBJECTIVE
To review the factors contributing to treatment resistance in hypertensive patients and assess the evidence from therapeutic trials in these patients.

DESIGN
A MEDLINE search using the words 'resistant hypertension', 'refractory hypertension' and 'treatment resistance, hypertension' was carried out to identify relevant articles. The bibliographies of articles were used to screen for other relevant articles. All available English-language articles on the epidemiology, prognosis and management of hypertension resistant to standard treatment were reviewed.

RESULTS
Resistant hypertension is an important public health problem and a common reason for referral of patients to specialized hypertension clinics. Patients with uncontrolled hypertension are at increased risk of stroke, myocardial infarction, congestive heart failure and renal failure. Many factors may play a role in the development of resistant hypertension, including misdiagnosis (pseudoresistance), noncompliance, occult secondary causes for hypertension, volume overload, obesity, cigarette smoking, excess alcohol intake, sleep apnea, interfering medications and suboptimal combinations of antihypertensives. Only beta-blockers and thiazide diuretics have been demonstrated to reduce cardiovascular morbidity and mortality in hypertension. The trials evaluating third-line agents in patients with resistant hypertension have demonstrated additional blood pressure lowering with all classes of agents, and the randomized controlled trials have not demonstrated any statistically significant differences between the agents in either efficacy or tolerability.

CONCLUSIONS
Evaluation of the patient with resistant hypertension should include 24 h ambulatory blood pressure monitoring and an extensive search for hypertensive end organ damage. Contributing factors should be sought and stepped care should still form the basis for treatment decisions. The choice of third-line agent should be dictated by the patient's renin profile, current medication and any concomitant diseases.


Hot air balloons are often made of lightweight material in order to improve the performance of such a craft. In this paper we discuss whether a hot air balloon made of lead could fly. We considered the lift generated by the heated air inside the balloon and concluded that a lead balloon could fly providing that the lead shell was less than 0.011mm thick.


[1] We study the polarization properties of the light field under a dynamic ocean surface using realistic linear and nonlinear ocean surface waves. The three-dimensional polarized radiative transfer of the dynamic ocean–atmosphere system is considered using a Monte Carlo vector radiative transfer simulation for arbitrary depth. The program is validated with measurement data taken in Hawaii during the Radiance in a Dynamic Ocean project. The main focus of this study is the influence of the wind-driven ocean waves on the polarization patterns and statistics at different optical depths under various conditions of light wavelength and solar incidence. Of special interest is the effect of the nonlinearity of the surface waves on the polarization statistics. To facilitate the study, phase-resolved direct simulations of the linear and nonlinear surface wavefields are performed using a high-order spectral method. The results show that the time-averaged degree of polarization within the Snell's window is dependent on the mean square slope of the ocean surface. Higher mean square slope, or wind speed, leads to a smaller degree of polarization. At the same time, the variability of the degree of polarization has a strong dependence on the surface roughness. A rougher ocean surface induces higher variability of the degree of polarization. The effect of wave nonlinearity can be neglected for the mean value of polarization, but is manifested in the variability of the degree of polarization, with a general increase in the variance with increasing wave nonlinearity. The present findings provide possible mechanisms for characterizing the dynamic ocean surface based on underwater polarized light measurements.


Space is not something just out there. It is a human construct, to which architecture can give lasting form. Taking this as a premise, this thesis has investigated the castellated architecture of Scotland, not as a military fortress or an expression of architectural genius, but as a structure where people lived and which influenced how they lived.

In achieving this aim, certain techniques of spatial analysis have been used, access analysis and planning diagrams, alongside a more experiential approach to the castle. The combination of these techniques has helped in providing an engagement with the material culture, which would not have been possible singularly. This engagement has been made all the richer for the extensive use of documentary sources to provide a context for the multitude of spatial relations which took place in and around the castle.

The castles which form the case-studies are Dirleton (East Lothian), Bothwell (Lanarkshire), Tulliallan (Fife), Morton (Dumfriesshire) and Elphinstone (East Lothian). The selection thus encompasses curtain wall castles, hall houses and tower houses.

The analysis has brought about a greater understanding of the individual case-studies. However, the conclusion reached about the nature of space within the castle has been widened out by relating the findings to other castles. Most interestingly, the analysis has suggested what one could call the 'privatisation of space' in late sixteenth century Scotland. This change in material culture coincided with dramatic religious, political and social changes.


This article argues that to understand the conditions that enable effective participation by women in politics, analysis is needed not just of the characteristics and performance of elected women leaders but also the extent to which village communities are engaged through collective processes, in demanding accountability from those elected. The article presents the experiences of a women's movement in the Uttarakhand that has evolved from a programme of environmental education in the region. Over the years, this movement has developed a strong political consciousness. Women's participation in Whole Village Groups has paved the way for active engagement with local governance institutions. The article concludes that by enabling collective spaces, reinforcing norms of equality and inclusiveness through debate and negotiation, building networks across villages and supporting each other through conflicts and confrontation, the organisations concerned have demonstrated that processes of collective empowerment can lead to effective political participation.


The paper presents a study of renovation of aerial aluminum alloy (LY12CZ) by laser melt casting with Al matrix composite powder. The microstructure of the melt casting zone was investigated, and the fatigue contrast test was carried out between the repaired specimens and the undamaged specimens. It is found that the melt casting zone consists of equiaxed crystals and columnar crystals. The equiaxed crystals distribute in the deposited layer and the crystal size is about 3~4μm. The columnar crystals whose axial direction size comes to 30μm~40μm exist near the interface with its crystallographic axis perpendicular to the interface. The fatigue life of specimens repaired by laser melt casting was shorter than no-damage specimens to a large extant, because of the flaws in the deposited layer engendered the origins of cracks; the columnar shape grains at the bottom of casting zone were easy to split under the tensile stress; the residual stress after the melt casting accelerated the initiation and growth of the cracks.


Sri Lankan women participation can be seen in every sphere of the country invarying degrees. However, in certain circumstances, it is likely to perceive that, avariety of constraints would hinder the women involvement and discriminate her in thesociety. Thus, the study mainly attempted to assert whether there is such kind ofconviction, which creates constraints for women to attain managerial positions in theprivate sector with special reference to Licensed Private Commercial banks in SriLanka. Accordingly, the study is focused to identify the perception of selectedorganizations on women participation in managerial positions as well as to find outwhether there is gender inequality in the composition of Managerial positions inselected organizations. In the study both the quantitative and qualitative approaches were used in orderto satisfy objectives of the study. Accordingly, 30 employees from 9 private commercialbanks including 8 domestic banks and 1 foreign bank which are located in the Colombocity were selected as the sample of the research by considering the convenience for datacollection and accessibility. Questionnaires were used as the main method for primarydata collection. Secondary data were gathered through published and unpublishedsources. In order to make quantitative and diagrammatical base for data analysis,Statistical Package for Social Sciences (SPSS 16.0) and Microsoft Office Excel 2007were used. The results revealed that, very limited female participation could be found in topmanagerial positions in the selected banks. Further, huge household responsibilities andlong office working hours, would lead working women to struggle in striking a balancebetween personal and work life, especially married women and females in extendedfamilies. When considering the context of working environment, discrimination could be observed in terms of salary and opportunities for career enhancement. Also in theorganizational perspectives, male employees are more likely to be positively perceivedby the banks rather than female employees. In conclusion, study reveals that the female employees in the private banks aremore likely to be kept in middle level positions whilst top positions are held by maleemployees, showcasing the gender inequality in the selected banks. Key words: Gender, Employment, Managerial positions, Licensed private commercialbanks


Abstract The Giant Gartersnake (Thamnophis gigas) is restricted to wetlands of the Central Valley of California. Because of wetland loss in this region, the Giant Gartersnake is both federally and state listed as threatened. We conducted mark–recapture studies of four populations of the Giant Gartersnake in the Sacramento Valley (northern Central Valley), California, to obtain baseline data on abundance and density to assist in recovery planning for this species. We sampled habitats that ranged from natural, unmanaged marsh to constructed managed marshes and habitats associated with rice agriculture. Giant Gartersnake density in a natural wetland (1.90 individuals/ha) was an order of magnitude greater than in a managed wetland subject to active season drying (0.17 individuals/ha). Sex ratios at all sites were not different from 1 ∶ 1, and females were longer and heavier than males. Females had greater body condition than males, and individuals at the least disturbed sites had significantly greater body condition than individuals at the managed wetland. The few remaining natural wetlands in the Central Valley are important, productive habitat for the Giant Gartersnake, and should be conserved and protected. Wetlands constructed and restored for the Giant Gartersnake should be modeled after the permanent, shallow wetlands representative of historic Giant Gartersnake habitat.


What accounts for the substantial variation in the temporal volatility of economic growth rates in democratic regimes? We claim that institutional differences between the majoritarian and proportional representation (PR) electoral systems explain why growth volatility is high in some democracies, but not others. Specifically, we suggest that unlike PR democracies, the pronounced career concerns of policymakers in majoritarian systems give them incentives to use their discretionary spending power to alter government spending levels sharply, which generates higher spending volatility in these countries. As a result, policymakers in majoritarian systems cannot credibly commit themselves to stabilizing spending levels. This causes uncertainty among economic actors about future spending levels and leads to unstable investment patterns that generate a higher volatility of growth rates in majoritarian democracies. Results from statistical models provide robust statistical support for our theoretical predictions.


The Wannier–Stark localization of miniband states has been investigated in an asymmetric double‐well superlattice. The period consists of 3.4 and 2.0 nm GaAs quantum wells separated by 1.4 nm Al0.15Ga0.85As barriers. Photocurrent spectra at 6 K reveal that the lowest excitonic peak near flat band splits up into eight peaks at moderate electric fields. At very high fields only one peak remains. The observed transitions are attributed to the Stark ladder splitting of the wide‐well miniband only. This type of superlattice introduces a new degree of freedom for the tailoring of electro‐optic devices.


Abstract Background The typical onset of schizophrenia coincides with the maturational peak in cognition; however, for a significant proportion of patients the onset is before age 18 and after age 30 years. While cognitive deficits are considered core features of schizophrenia, few studies have directly examined the impact of age of illness onset on cognition. Methods The aim of the study was to examine if the effects of age on cognition differ between healthy controls (HCs) and patients with schizophrenia at illness onset. We examined 156 first-episode antipsychotic-naïve patients across a wide age span (12–43 years), and 161 age- and sex-matched HCs. Diagnoses were made according to ICD-10 criteria. Cognition was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS), and IQ was estimated using subtests from the Wechsler adult- or child-intelligence scales. Multivariate analysis of covariance (MANCOVA) was used to examine linear and quadratic effects of age on cognitive scores and interactions by group, including sex and parental socioeconomic status as covariates. Results There was a significant overall effect of age on BACS and IQ (p < 0.001). Significant group-by-age interactions for verbal memory (for age-squared, p = 0.009), and digit sequencing (for age, p = 0.01; age-squared, p < 0.001), indicated differential age-related trajectories between patients and HCs. Conclusions Cognitive functions showing protracted maturation into adulthood, such as verbal memory and verbal working memory, may be particularly impaired in both early- and late-schizophrenia onset. Our findings indicate a potential interaction between the timing of neurodevelopmental maturation and a possible premature age effect in late-onset schizophrenia.


Self-focusing by a Kerr nonlinearity in combination with an intracavity aperture creates a power-dependent loss in lasers, which has been used as a method for passive mode locking of lasers. An analytical treatment is presented that yields closed-form expressions for the modulation efficiency. Comparisons between analytical results and numerical calculations are performed. General features of this mode-locking technique are discussed, and a procedure for the optimization of hard-aperture Kerr-lens mode-locking performance is given.


OBJECTIVE
North Rhine-Westphalia (NRW's) indicator set for health reporting activities comprises more than 70 regional health indicators, which means that these data are available for health reporting purposes for all 54 districts and urban districts. Morbidity and mortality indicators differ in part quite considerably and require further interpretation. With the help of selected indicators, the authors of the following article try to explain the relation between social status and health status.

METHODOLOGY
Ten years ago, NRW, as part of its health reporting activities, started to carry out multivariate analyses to classify socio-demographically different types of regions, leading to the establishment of six types of regions which can be linked to health-related data. Social structure indicators are part of a first step submitted to a main component analysis and grouped together by a small number of features and/or factors which clearly reflect differences in living conditions. As a result, two factors were extracted: an economic prosperity factor which is mainly determined by the disposable income and a so-called A-factor which mainly describes the fact that poorer, elderly, unemployed and foreign population groups live concentrated in regions with a declining population but high population density. These factors are, in a second step, used for a cluster analysis aimed at classifying the 54 districts and urban districts and at establishing different types of regions. In a subsequent step, the cluster method is used to explain regional variations of selected health indicators.

RESULTS
It is a proven fact that morbidity and mortality are influenced by social status. With the help of selected indicators, six clusters with a different socio-economic structure influencing the health status of the population can be established for NRW. Special attention should be paid to the cluster of the Ruhr area with its below-average social situation. With 90% NRW's population primarily living within the other 5 clusters which are differently structured but increasingly adjusting their living conditions to each other. The authors of this publication assign four health status indicators to predefined clusters and analyse the relation between the social and health status: female and male life expectancy, the proportion of underweight live births, infant mortality and avoidable deaths.In regions with high A-factor values (poverty pole), i. e., in several ways socially deprived regions, male and female average life expectancy is significantly lower than in regions with a clearly less pronounced accumulation of problems. Moreover, a significantly higher life expectancy for male live births can be observed in regions with a high disposable income. The model fails to establish a convincing correlation between social status and infant mortality and breast cancer.

CONCLUSIONS
Knowledge about socio-demographic differences in the health status of the population is particularly important for prevention measures in order to be able to react appropriately to health risks in districts and urban districts. The analysis shows that an intense regional accumulation of problems will have a negative influence on health status, an influence which is more significant than the positive influence of prosperous regions on the health status.


The influence of nonselective and selective alpha-adrenergic agonists on intraocular pressure (IOP) was studied in isolated arterially perfused rabbit eyes. Drugs were given intra-arterially or topically. With either route of administration, no initial hypertensive phase was observed after l-epinephrine, l-norepinephrine, l-phenylephrine (alpha 1), or methoxamine (alpha 1), but there was an immediate ocular hypotensive effect. The alpha 2-agonist B-HT 920 caused a nonsignificant 1 mm Hg fall in IOP.


Background: Health behaviours are consolidated and modified throughout human life; however, adolescence is a significant stage in the process of acquiring them. One of the identifiers of the represented health behaviours is a proper level of body fat influenced by selfassessment of own image. Material/Methods: The authors considered relationships between the real image, health behaviours and selfassessment of own appearance; these were analysed using a sample of randomly selected 830 adolescents. The body composition analysis was conducted by means of bioelectrical impedance, assessment of self-image was done with Stunkard's Figure Rating Scale, and assessment of health behaviours was done with Juczyński's Health Behaviour Inventory. Results: The mediatory role of health behaviours between the actual body outline and the selfassessment of body image as well as the desired body was not observed; nonetheless, most of the respondents wanted a slimmer body. Conclusions: The observed difference between self-assessment of the real and the desired body and the related consequences for physical and psychological health encourage one to include promotion of a positive body image itself to stabilize high body self-esteem.


Pancreatic β-cells secrete insulin in response to closure of ATP-sensitive K+ (KATP) channels, which causes membrane depolarization and a concomitant rise in intracellular Ca2+ (Cai). In intact islets, β-cells are coupled by gap junctions, which are proposed to synchronize electrical activity and Cai oscillations after exposure to stimulatory glucose (>7 mM). To determine the significance of this coupling in regulating insulin secretion, we examined islets and β-cells from transgenic mice that express zero functional KATP channels in approximately 70% of their β-cells, but normal KATP channel density in the remainder. We found that KATP channel activity from approximately 30% of the β-cells is sufficient to maintain strong glucose dependence of metabolism, Cai, membrane potential, and insulin secretion from intact islets, but that glucose dependence is lost in isolated transgenic cells. Further, inhibition of gap junctions caused loss of glucose sensitivity specifically in transgenic islets. These data demonstrate a critical role of gap junctional coupling of KATP channel activity in control of membrane potential across the islet. Control via coupling lessens the effects of cell–cell variation and provides resistance to defects in excitability that would otherwise lead to a profound diabetic state, such as occurs in persistent neonatal diabetes mellitus.


A novel matrix solution is developed for the zero-sum game concerning uncertain information. Specifically, a new functional model for the game with grey information is introduced, which contains uncertain variables because of information shortage. Additionally, the matrix solution is designed for the functional model in which the players' optimal probabilities of mixed strategies and optimal profits can be obtained by the matrix operation. Finally, the case of mobile phone market development is conducted to verify the effectiveness of the above method.


Fertilization involves the production of inositol trisphosphate and diacylglycerol with a subsequent increase in intracellular calcium concentration ([Ca2+]i) and the activation of a calcium-dependent protein kinase, the so-called protein kinase C (PKC). Methods of parthenogenetic activation have focused on this calcium wave which seems to be large enough to generate all the responses associated with fertilization and even finally inducing the activation of PKC activity. The specific stimulation of PKC by phorbol esters in turn elicits [Ca2+]i oscillations although no reports exist claiming that the mere activation of this protein is capable of sustaining embryonic development. In this paper we describe the effect of different calcium ionophores and phorbol esters as parthenogenetic agents on mouse oocytes compared with ethanol as the standard procedure. Phorbol esters (OAG) fail to activate a significant number of oocytes, with very few reaching blastocyst stage. However, when a calcium ionophore (A23187) is added, the percentage of embryos reaching the blastocyst stage increases to such an extent that it is the best chemical method assayed to date. We conclude that incubation with both compounds combined inhibits feed-back processes between the above reactions and so induces a more physiologic parthenogenetic activation.


Performance analysis via stochastic simulation is often subject to input model uncertainty, meaning that the input model is unknown and needs to be inferred from data. Motivated especially from situations with limited data, we consider a worst-case analysis to handle input uncertainty by representing the partially available input information as constraints and solving a worst-case optimization problem to obtain a conservative bound for the output. In the context of i.i.d. input processes, such approach involves simulation-based nonlinear optimizations with decision variables being probability distributions. We explore the use of a specialized class of mirror descent stochastic approximation (MDSA) known as the entropic descent algorithm, particularly effective for handling probability simplex constraints, to iteratively solve for the local optima. We show how the mathematical program associated with each iteration of the MDSA algorithm can be efficiently computed, and carry out numerical experiments to illustrate the performance of the algorithm.


As activity-based approaches gain acceptance for travel demand analysis and forecasting in practice, the unit of analysis in transportation planning models needs to shift from a one-way trip to an activity schedule with associated trip chains. A spatial network assignment process and its application to an actual network are described; the process can be used in conjunction with activity-based travel demand forecasting procedures as well as for traffic operational studies. Two simulation-based dynamic spatial microassignment procedures for travel demand with activity trip chains are presented. The first represents a one-step simulation-assignment procedure in which assignment of trips is based on prevailing travel time. The second is an iterative simulation-assignment procedure in which a user equilibrium solution is obtained. The models are illustrated through various experiments conducted using an actual network (in Fort Worth, Texas) to examine network performance under different activity and trip-chaining scenarios. Different demand levels with different trip chain patterns are considered and compared for an actual transportation network. In addition, a case is made for dynamic microassignment of activity trip chains by contrasting it with current practice and illustrating the pitfalls of inappropriately recognizing trip chains using current-practice assignment. In particular, two different procedures are considered and compared for selected test scenarios with the dynamic assignment models presented. The first procedure corresponds to the case in which the activity and trip-chaining behavior is completely ignored, and only the final destination in the chain is considered. The second procedure treats the links of the chains separately as independent trips, without appropriate linkage between them.


Surgical resection is the most frequent curative treatment proposed to patients with head and neck cancers. It is currently integrated into specific therapeutic schemes and therapeutic stratification, but the surgical procedure itself as well as its evaluation do not rely on tumor biology. Here, we present a number of recent studies, mostly based on system analyses and genomics, that show how tumor analyses could help to: i) define the indications and the extent of surgical resections; ii) personalize the perioperative management; iii) facilitate the detection of post-surgical tumor recurrence. Overall, these studies provide a proof of principle that precision surgery, i.e. based on tumor biology, similarly to precision medicine, is applicable to head and neck cancers.


As the single-signal carrier frequency estimation method is unsuitable for the time–frequency overlapped signals in an underlay cognitive radio network (CRN), in this paper, we propose a novel carrier frequency estimation method for the time–frequency overlapped multi-level amplitude-shift keying (MASK) signals in the underlay CRN. In this method, the diagonal slice spectrum of cyclic bispectrum for the time–frequency overlapped MASK signals is first estimated, and then, the carrier frequency of component MASK signals is estimated by extracting the position information of the diagonal slice spectrum line based on the norm theory and the adaptive threshold. In addition, the Cramer–Rao bound (CRB) of the carrier frequency estimation for the time–frequency overlapped MASK signals is also derived. The simulation results show that the proposed method can estimate the carrier frequency of the time–frequency overlapped MASK signals effectively, especially in low signal-to-noise ratio (SNR) regions.


Why are forced displacement, ethnic cleansing and genocide an enduring feature of state systems? In this book, Heather Rae locates these practices of 'pathological homogenisation' in the processes of state building. Political elites have repeatedly used cultural resources to redefine bounded political communities as exclusive moral communities, from which outsiders must be expelled. Showing that these practices predate the age of nationalism, Rae examines cases from both pre-nationalist and nationalist eras: the expulsion of the Jews from fifteenth century Spain, the persecution of the Huguenots under Louis XIV, and in the twentieth century, the Armenian genocide, and ethnic cleansing in former Yugoslavia. She argues that those atrocities prompted the development of international norms of legitimate state behaviour that increasingly define sovereignty as conditional. Rae concludes by examining two 'threshold' cases - the Czech Republic and Macedonia - to identify the factors that may inhibit pathological homogenization as a method of state-building.


Elsevier is the world's largest scientific publishing company. It owns a database
named Scopus that stores a multitude of scientific papers, books and manuscripts.
Besides scientific documents, author's profiles are also stored. Author's profiles contain
information such as documents published and the number of citations that an
author gets on his works from other scientific publication. Sometimes scientific articles
are missing or the number of citation can be lower than the author expected.
There are several reasons why a scientific report is missing in the author profile or
the number of a citation can be lower than expected. One of those is because the
document can be out of policy and therefore not yet referenced in the database. In
such cases the author can contact the Scopus customer service by email including
the reference of the missing scientific document. These references are written within
the text of the email using several styles and are often incomplete. Sometimes the
year of publication is missing, only the first author is mentioned, or the title is not
complete.
Elsevier is developing a technology that aims to support the Customer Service operator
to a faster understanding of the problem behind a missing scientific document
record. In order to understand and automate those problems, such as automatic
recognition out of policy papers, the machine has to be able to understand which
documents are referenced within the text of the emails. In order to extract the right
entities and retrieve the correct document mentioned in the free text, such as emails
or web forms, this research project has been divided into three main steps. The first
step is to identify the parts of a text that refer to a bibliographic referent, the reference
text. The second step is to identify the components of a reference text or references'
entities, e.g. author name(s), title, year of publication, journal name, etc. The third
step is to find a match with the referent in the text and the real document according
to the components identified.
All of the above have led to the following question: can each of these steps be done
fully automatically using machine learning approaches in order to retrieve the correct
scientific document included by the reference in the email?
This report presents the answer to this question. It focuses on references' entities
recognition in emails data, considered free text. It has been found that narrowing
down the problem by dividing and classifying the email's sentences that contain
the references and subsequently performing entities extraction on these sentences,
it is possible to obtain a good performance in terms of the reference entities extraction.
By having good accuracy on entities recognition it is possible to recognize and
retrieve the corrected scientific document mentioned within an unstructured (free)
text.


Sea-level rise, a consequence of climate change, is progressively affecting coastal areas around the globe. In turn, protected areas are keystones for protecting coastal biodiversity and the ecosystems services ensuring sustainable livelihoods. Effective management and adaptation plans are needed to maintain ecological function and integrity. In the present article, we used a coastal digital elevation model to simulate inundation surfaces and a prioritization index for ranking management interventions in 278 coastal protected areas from 27 African countries. Of these, 15 areas and eight countries demonstrated a high need for proactive management actions because of high levels of biodiversity, international conservation relevance, and exposure to sea-level rise. From the array of management actions available, tailored solutions are being implemented according to the morphology and location of the areas. Concerted action by international, government, and local partners is required for successful protection of the areas, including implementation of adaptive plans and monitoring progress schemes.


Cysteine was introduced from residues 116 to 121 of the γ subunit of the fetal mouse acetylcholine receptor, and the mutant receptors were treated with methanethiosulfonate reagents and examined for changes in ligand binding properties. Of the 18 combinations of mutant and reagent, only receptors harboring γL119C treated with the quaternary ammonium reagent MTSET (trimethylammonium-ethyl methanethiosulfonate) show a decreased number of α-bungarotoxin (α-btx) sites. The decrease of 50% suggests that α-btx binding to the site harboring γL119C is blocked. Analysis of binding of the site-selective ligands dimethyl-d-tubocurarine (DMT) and α-conotoxin M1 (CTX) confirm specificity of modification for the site harboring γL119C. Cysteines placed at equivalent positions of the δ and ε subunits also lead to selective loss of α-btx binding following MTSET treatment. γL119C receptors treated with the primary amine reagent MTSEA (aminoethyl methanethiosulfonate) retain α-btx binding to both sites but show reduced affinity for DMT and CTX at the modified site. Lysine mutagenesis of Leuγ119, Leuδ121, and Leuε119 mimics MTSEA treatment, whereas mutagenesis of Thrα119 and Glnβ119 is without effect, demonstrating subunit and residue specificity of MTSEA modification. MTSET modification of nearby γY117C does not block α-btx binding but markedly diminishes affinity for DMT and CTX. The overall findings indicate a localized point of interaction between α-btx and the modified γL119C, δL121C, and εL119C.


The thermoluminescence (TL) of neodymium-doped gallium sulfide (GaS:Nd) single crystals was measured from 10 K to room temperature with various heating rates between 0.2 and 1.0 K/sec. Two peaks centered at 70.9 K and 116.0 K were observed when using a heating rate of 0.8 K/sec. Initial rise and curve fitting methods were used to obtain information on trap activation energies. Activation energies of 94 and 216 meV were found for two analyzable peaks. The heating rate dependencies of TL intensities revealed that one of the observed peaks showed normal behavior according to the one trap-one recombination model, whereas the other model showed anomalous heating rate behavior. TL experiments were also carried out at different illumination temperatures from 10 to 32 K; maximum peak temperature remained almost the same at various illumination temperatures. This behavior indicated that the revealed trapping centers are single, discrete levels. The TL glow curves of undoped GaS crystals were also investigated and the effect of Nd doping on the TL characteristics of crystals is discussed in the manuscript.


Building on the records life-cycle concept the research explored business records management practices in nine exporting companies in the Iringa region of Tanzania. Various records management models were examined and a hybridized records life-cycle theory was proposed and used as the framework for the investigation. The study used interviews protocols and observations schedules to collect primary data from nine exporting companies in the Iringa region. The empirical part of the study revealed that business records in both electronic and paper formats were not adequately managed through their entire life span. There was an urgent need for the management of business records throughout their life-cycle in order to support strategic business objectives and preserve corporate memory.


Business Process Modelling Notation (BPMN) is a way to graphically draw a diagram of a business process. A BPMN diagram consists of several so-called flow objects. These are interconnected in the graph through sequence flows. BPMN models are merely graphical representations of business process and there is a need to simulate these diagrams for different purposes. The simulation that now is available for BPMN is that the model is evaluated by checking if it is correct. To evaluate these models more precise the specification has been extended by our principals to include workers and tasks. By simulating the diagram and obtaining data based on the various attributes defined for the workers and the tasks, conclusions can be drawn concerning the optimal assignment. In order to design and simulate a ow chart according to BPMN specification an editor and simulator was implemented in Java. The simulator is implemented based on the principle of discrete event simulation (DES). When the flow reaches a flow object it is executed which among others means that possible future events are generated and added to the future event queue. The simulator continues the execution by selecting the future event with the smallest timestamp. In this way the simulator traverses the graph until the future event list is empty which is when the ow reaches a final event. Since it is now possible to model BPMN diagrams according to own preferences, a large number of different graphs can be simulated. BPMN diagrams model made in other applications and exported using the XPDL-standard can also be loaded. The program with the simulator and editor were evaluated using two different models and optimization algorithms. The results from these two evaluations indicates that the developed program is performing in comparison with the expected result.


Although typically associated with onset in young adults, multiple sclerosis (MS) also attacks the elderly, which is termed late‐onset MS. The disease can be recapitulated and studied in a mouse model, experimental autoimmune encephalomyelitis (EAE). The onset of induced EAE is delayed in aged mice, but disease severity is increased relative to young EAE mice. Given that CD4+FoxP3+ regulatory T (Treg) cells play an ameliorative role in MS/EAE severity, and the aged immune system accumulates peripheral Treg (pTreg) cells, failure of these cells to prevent or ameliorate EAE disease is enigmatic. When analyzing the distribution of Treg cells in EAE mice, the aged mice exhibited a higher proportion of polyclonal (pan‐) pTreg cells and a lower proportion of antigen‐specific pTreg cells in the periphery but lower proportions of both pan‐ and antigen‐specific Treg cells in the central nervous system (CNS). Furthermore, in the aged inflamed CNS, CNS‐Treg cells exhibited a higher plasticity, and T effector (CNS‐Teff) cells exhibited greater clonal expansion, disrupting the Treg/Teff balance. Transiently inhibiting FoxP3 or depleting pTreg cells partially corrected Treg distribution and restored the Treg/Teff balance in the aged inflamed CNS, thereby ameliorating the disease in the aged EAE mice. These results provide evidence and mechanism that accumulated aged pTreg cells play a detrimental role in neuronal inflammation of aged MS.


We report a case of multiorgan failure resulting from treatment with the antiviral foscarnet in a kidney transplant recipient. Precipitation of foscarnet crystals was confirmed histologically from a biopsy of the transplant using optical and infrared microscopy. In addition to kidney damage resulting from foscarnet crystal precipitation in the tubular lumen and glomerular capillaries, the patient presented with pancreatitis, pancolitis, and myocarditis with shock. Interruption of the treatment led to rapid improvement in her general condition, but did not prevent permanent loss of the kidney transplant. When faced with unexplained multiorgan failure in a patient treated with foscarnet, one should assume this substance to be toxic. A kidney biopsy can confirm this diagnosis.


Abundant quantities of beechwood forest residues and industrial residues represent a potentially valuable raw material. Different options for the chemical processing of biomass to marketable products, as well as relevant technologies, are presented in this paper. Beechwood can be efficiently converted to platform chemicals and fuels, such as ethanol and butanol. Sophisticated delignification procedures enable energy efficient and environmentally friendly production of cellulose fibers to be used for paper and textiles, as well as to manufacture nanofibrillated and nanocrystalline cellulose. Wood fibers are suitable for the preparation of wood plastic composites, with a wide range of potential applications. Likewise, hemicellulose and lignin fractions may be conveniently used. Chemical conversion of biomass takes place within biorefineries.


EEG has been the primary diagnostic tool in clinical epilepsy for nearly a century. Its review is performed using qualitative clinical methods that have changed little over time. However, the intersection of higher resolution digital EEG and analytical tools developed in the last decade invites a re-exploration of relevant methodology. In addition to the established spatial and temporal markers of spikes and high frequency oscillations, novel markers involving advanced post-processing and active probing of the interictal EEG are gaining ground. This review provides an overview of the EEG-based passive and active markers of cortical excitability in epilepsy and of the techniques developed to facilitate their identification. Several different emerging tools are discussed in the context of specific EEG applications and the barriers we must overcome to translate these tools into clinical practice.


The advent of off-the-shelf chimeric antigen receptor (CAR) T cell therapeutics is widely recognized to be a major potential advancement for the treatment of cancer. Several obstacles currently hamper the broad use of CAR T cells, including the inherent variability and cost of manufacturing of autologous cellular populations, the absolute requirement for precise genetic editing in the allogeneic setting, and the challenge to keep pace with clonal heterogeneity. Here we present pre-clinical data for FT819, a first-of-kind off-the-shelf human induced pluripotent stem cell (hiPSC)-derived CAR T cell product. FT819 is defined by the precise genetic engineering of multiple targeting events at the single cell level to create a clonal master iPSC line. The engineered features include the targeted integration of a novel, modified CD19 CAR into the T cell receptor α (TRAC) locus to provide antigen specificity and enhanced efficacy while eliminating the possibility of graft versus host disease (GvHD), and the expression of a high-affinity, non-cleavable form of CD16 (hnCD16) to deliver an adjustable system to address tumor antigen escape.
 Through a proprietary cellular reprogramming platform, peripheral blood derived T cells are converted to hiPSCs, engineered to contain the modified CD19 CAR targeted into the TRAC locus and hnCD16, and clonally selected to create a master hiPSC line (TRAC-TiPSC, FT819). Molecular characterization of the TRAC-TiPSC master cell line by 5' junction, 3' junction and internal sequence PCR confirmed homology directed repair and bi-allelic targeting of the CD19 CAR into the TRAC locus. The origin of the clonal master cell bank was confirmed to be a TCRαβ T cell by PCR-mediated detection of TCRδ locus deletion and methyl-seq analysis of the TCRα locus. Flow cytometric analysis demonstrated the maintenance of a uniform population of hiPSCs (>95% SSEA4/TRA-1-81/OCT4/NANOG) and expression of hnCD16 transgene (>95% CD16).
 Utilizing our stage-specific T cell differentiation protocol, we demonstrate that the TRAC-TiPSCs yield TRAC-iT cells with uniform expression of the CAR (>95%), complete elimination of TCR surface expression and clinically enabling expansion through the manufacturing process (>50,000 fold). To confirm the lack of alloreactivity conferred by the deletion of endogenous TCR expression, mixed lymphocyte reactions were performed using TRAC-iT, primary TCR+ T cells and primary TCR+CAR+ T cells as responders and HLA-mismatched peripheral blood mononuclear cells (PBMCs) as targets. In comparison to primary T cells and primary CAR-T cells, TRAC-iT did not respond and proliferate in response to TCR stimulation or HLA-mismatched PBMCs indicating that the risk of GvHD was alleviated.
 In vitro functional studies established that TRAC-iT possess a potent cytotoxic T lymphocyte response to CD19 antigen challenge in a similar manner to peripheral blood CAR T cells as demonstrated by expression of markers indicative of degranulation (CD107a/b, Granzyme B), T cell activation (CD69, CD25), and production of INFγ, TNFα and IL2. Importantly, TRAC-iT targeted tumor in an antigen specific manner as verified by lysis of CD19+, but not CD19-, tumor cell lines as seen by in vitro cytolytic assays (50% killing E:T; TRAC-iT = 1:8, primary CAR-T = 1:4).
 In vivo studies demonstrated that TRAC-iT cells effectively control tumor progression in a mouse model of acute lymphoblastic leukemia Nalm6 (TRAC-iT versus no treatment, p<0.0001). To validate the capability of TRAC-iT to simultaneously target multiple antigens, TRAC-iT was co-cultured with mixtures of CD19+CD20+ and CD19-CD20+ tumor cells in the presence of anti-CD20 monoclonal antibody, Rituxan. In vitro cytolytic assays demonstrate that only TRAC-iT cells can effectively identify and eliminate CD19-CD20+ tumor cells when combined with Rituxan. Importantly, the antibody-dependent cellular-cytotoxicity did not appear to interfere with CAR function as TRAC-iT maintained its directed cytotoxic capacity. Collectively, these preclinical studies suggest that FT819 is a consistent and uniform off-the-shelf product than can be effectively and safely used in the treatment of B cell malignancies in the allogeneic setting.

 Clarke: Fate Therapeutics Inc.: Employment. Chang:Fate Therapeutics Inc.: Employment. Husain:Fate Therapeutics Inc.: Employment. Lai:Fate Therapeutics Inc.: Employment. Peralta:Fate Therapeutics Inc.: Employment. Stokely:Fate Therapeutics Inc.: Employment. Abujarour:Fate Therapeutics Inc.: Employment. Dinella:Fate Therapeutics Inc.: Employment. Lee:Fate Therapeutics Inc.: Employment. Pribadi:Fate Therapeutics Inc.: Employment. Chu:Fate Therapeutics Inc.: Employment. Truong:Fate Therapeutics Inc.: Employment. Sabouri-Ghomi:Fate Therapeutics Inc.: Employment. Meza:Fate Therapeutics Inc.: Employment. Riviere:Juno Therapeutics, a Celgene Company: Membership on an entity's Board of Directors or advisory committees, Research Funding; Fate Therapeutics Inc.: Research Funding. Sadelain:Juno Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; Fate Therapeutics Inc.: Research Funding. Valamehr:Fate Therapeutics Inc.: Employment.


ABSTRACT Animal hoarding not only presents significant welfare issues for the animals involved, but also for the hoarders and people in the surrounding community. Existing studies on the issue have primarily been undertaken in the USA and little is known about animal hoarding in other countries, including Australia. It has been estimated that the per-capita prevalence of animal hoarding in Victoria, Australia, is similar to that in the USA, but in order to design effective intervention strategies, the extent of the issue and its characteristics need to be identified. This study analyzes data from 22 recent cases of animal hoarding from a number of agencies in Victoria. The demographics and living conditions of animal hoarders in Victoria and the USA were found to be similar. In contrast, the animals involved in hoarding cases in Victoria were in a better condition than the animals in the USA, with behavioral issues being the leading animal welfare concern in Australia. Behavioral problems resulted in euthanasia of the animals in 45% of the cases studied. All of the agencies included in this study call for a greater involvement or support from human mental health services to fully address the root of the problem. The information from this study can be used to help identify groups at risk to develop effective and appropriate means of prevention of, and intervention in, animal hoarding cases.


Low temperature soldering has been realized to create a strong metallurgical interconnection between Cu using the self-propagating exothermic reaction by Al–Ni NanoFoil. This technique presents a great potential for electronics integration with a significantly reduced processing temperature (at least 150 °C lower than traditional techniques) and minimal thermal effects to the components. In this study, finite element analysis was performed to predict the temperature profiles across bonding interfaces, which were subsequently correlated with the formation and quality of the bonded structures. It has been revealed that, for nonequilibrium nanosized phases and defects, their formation and distribution were primarily attributed to the solid–liquid interdiffusion and rapid solidification, under the highly transient regime due to a drastic heating/cooling (105–107  °C/s). The preheating and pressure applied to the bonding structure were clearly beneficial to improve the quality of bonding. This was achieved by the thinned solder thickness and the correspondingly improved temperature profiles that enable a sufficient wetting, filling, and interfacial reactions. Through the comparative analysis of the numerical predictions and the experimental results, the solder layers must completely melt across their thickness and have a total heat over 30 K ms on the Cu to ensure robust interconnections with a shear strength of approximately 37 ± 3 MPa and dense continuous bonding interfaces.


IPMC (ionic polymer metal composite), a kind of ionic electroactive polymer (EAP) has wide applications in the filed of bionics and artificial apparatus for its fast and large bending deformation under the low driving voltages. In this paper, thick IPMCs with various numbers of films were first fabricated by the hot-pressing method. Then the effect of the thickness on its properties, such as the tip forces and water uptake capability, were investigated. The effect of length of the IPMC on its tip forces was further studied. SEM (scanning electron microscopy) micrographs of IPMC specimen were also examined.


Perhaps it is because of our general disregard of its importance as a disease that so little work has been done on the morphology of the blood in epidemic parotitis. From such a viewpoint it is true that a perfect knowledge of the pathological physiology of the disease is of comparative little import. But this disease, it has been observed, is accompanied by a lymphocytosis, and the problem of lymphocytosis is an interesting and important one. The blood-picture of this disease is also of distinct value in differential diagnosis. A perusal of the literature on the blood-picture in this disease shows it to be very fragmentary; so that there is need for summarizing and a proper correlation of the results obtained by the various observers. Since the work of Wile, 1 I have been unable to find any noteworthy contributions. Wile's bibliography refers to the work of Cabot, 2 who


In January 2011, a sequence of earthquakes occurred in close proximity to a well, which was being hydraulically fractured in south‐central Oklahoma. The hydraulic fracturing of the Picket Unit B Well 4–18 occurred from 16 January 2011 18:43 through 22 January 16:54 UTC. This vertical well penetrated into the mature Eola‐Robberson oil field. Earthquakes were identified by cross correlating template waveforms from manually identified earthquakes and cross correlating these templates through the entire operation period of the Earthscope USArray Transportable Array (TA) station X34A. This produced a series of 116 earthquakes, which occurred from 17 January 2011 19:06 through 23 January 3:13 UTC with no other similar earthquakes identified at other times prior to or post‐hydraulic fracturing. The identified earthquakes range in local magnitude ( M L) from 0.6 to 2.9, with 16 earthquakes M L 2 or greater and a b ‐value of 0.98. There is a strong temporal correlation between hydraulic fracturing and earthquakes. This correlation is strengthened because hydraulic fracturing operations ceased for ∼2 days due to bad weather, and earthquakes can be observed to cease during this period and resume after hydraulic fracturing had resumed. Earthquakes were relocated using cross‐correlated phase arrivals and bootstrap iterations of hypoDD. Locations were well constrained for 86 earthquakes. These earthquake locations clearly delineate a fault which strikes ∼166°, subparallel to the mapped minor fault sets in the area, and dips steeply to the west. The earthquakes appear to have occurred at shallow depths from ∼2 to 3 km and within ∼2.5  km horizontally of the well. The first earthquake occurred ∼24 hrs after hydraulic fracturing began at the well. This delay is consistent with the diffusion of pore pressure in the subsurface over a distance of ∼2  km.

Online Material: Results from bootstrap hypoDD relocations using cross‐correlation phase arrivals.


Bio-pellet is an important fuel for sustainable energy in future and a potential
renewable energy substitute for rural areas, East Java of Indonesia in particular. One
of the candidates for solid fuel is coffee husk pellets, it is a bio-product produced from
coffee production waste. In this research, focus is on hole design of stove that could
be used for generating energy from coffee husk pellet generally used as feedstock.
This designed device also could be used as an alternative for gas-powered stoves. The
variations in stove designs were proposed and has been modified as required. It is
conducted in the stove's combustion cylinder. A particular stove (OS1) was used as
control and other stoves were tested to measure the heat, thermal efficiency and
emissions. The heat was produced at 316,880 kJ, 310,601 kJ, 308,229 kJ, and 306,833
kJ for stoves of 40, 20, 10 hole variation and OS1, respectively. Thermal efficiency for
#OTHER stove were 16.47%, 16.39% for 10 holes, 15.96% for 20 holes of and 15.38%
for 40 holes, respectively. The emissions results obtained were 333ppm for OS1, 298
ppm for 10 holes, 289 ppm for 20 holes, and 273 ppm for 40 holes of stove,
respectively. As a conclusion, the stove with 40 holes variation, is selected as the most
desired for this type of pellet stove.


Abstract We observed a pair of Belted Kingfishers (Megaceryle alcyon) as they initiated burrow excavation in a bank along Rattlesnake Creek near Missoula, Montana in April 2010. During 180 min of observation on the first three mornings (17–19 Apr) of burrow excavation we observed the kingfishers fly rapidly at the bank from perched or hovering distances of 1–3 m and strike the bank bill-first 176 times, forming a pit in the vertical bank about body-deep after 60 hrs of work. Both sexes performed aerial ramming, at roughly the same rate. On the fourth morning we saw no ramming during 40 min of observation while excavation continued, but the site was abandoned later in the day. Aerial ramming at the start of burrow excavation appeared necessary because (1) the bank was vertical to overhanging without exposed roots, providing no opportunity for the birds to perch at the excavation site when beginning to dig, and (2) the birds seemed unable to strike the substrate with sufficient force to promote excavation while perched on the bank or hovering at the burrow entrance until several days into excavation, perhaps due to the presence of imbedded gravel and cobble in the soil. At least 13 species of kingfishers in the subfamilies Alcedininae and Daceloninae are reported to aerial ram into potential burrow sites (banks, termitaria, trees). Ours appears to be the first report of aerial ramming by the Belted Kingfisher and a member of the subfamily Cerylinae.


Pocket Guide for Lactation Management, Second Edition is the perfect resource for the variety of situations commonly encountered by those working with lactating and breastfeeding mothers and their babies. Conveniently organized by the issue that the healthcare provider will meet, it helps caregivers quickly resolve key challenges, such as babies who aren't gaining weight fast enough, mothers with sore nipples, and basic sucking problems. Quick reference charts, algorithms, and diagrams assist the caregiver in quickly determining whether they have assessed the situation correctly. Designed for use by an interdisciplinary array of caregivers in practice settings, Pocket Guide for Lactation Management, Second Edition contains updated references, new evidence-based strategies for problem resolution, and a user-friendly appendix.


Spinal Cord Injury (SCI) is a common neurological disorder with devastating psychical and psychosocial sequelae. The majority of patients after SCI suffer from permanent disability caused by motor dysfunction, impaired sensation, neuropathic pain, spasticity as well as urinary complications, and a small number of patients experience a complete recovery. Current standard treatment modalities of the SCI aim to prevent secondary injury and provide limited recovery of lost neurological functions. Stem Cell Therapy (SCT) represents an emerging treatment approach using the differentiation, paracrine, and self-renewal capabilities of stem cells to regenerate the injured spinal cord. To date, multipotent stem cells including mesenchymal stem cells (MSCs), neural stem cells (NSCs), and hematopoietic stem cells (HSCs) represent the most investigated types of stem cells for the treatment of SCI in preclinical and clinical studies. The microenvironment of SCI has a significant impact on the survival, proliferation, and differentiation of transplanted stem cells. Therefore, a deep understanding of the pathophysiology of SCI and molecular mechanisms through which stem cells act may help improve the treatment efficacy of SCT and find new therapeutic approaches such as stem-cell-derived exosomes, gene-modified stem cells, scaffolds, and nanomaterials. In this literature review, the pathogenesis of SCI and molecular mechanisms of action of multipotent stem cells including MSCs, NSCs, and HSCs are comprehensively described. Moreover, the clinical efficacy of multipotent stem cells in SCI treatment, an optimal protocol of stem cell administration, and recent therapeutic approaches based on or combined with SCT are also discussed.


Conventional wisdom suggested that investment flows in where you have abnormal returns that resulted in a high productivity area. However, FDI behaves peculiarly, as most are targeted towards developed countries where excess competition drives down returns and ultimately productivity. On the contrary, it shy in developing countries where one has more productive investment opportunities. This study tries to tackle the problem and explores the factors that influenced FDI flows. In particular, we focused on productivity, trade openness, financial liberalization, and institutions. Macro-level data was collected from 27 economies from 2004 to 2015. The analysis was done using GMM methodology. The results showed productivity remained insignificant in explaining FDI throughout the models. Trade seems to have a significant positive impact on the model without the interaction effect. Interestingly, financial liberalization seems to affect FDI negatively in all cases. GDP growth had a positive and significant effect. All Institutional variables that include control of corruption, government effectiveness, regulatory quality, rule of law, seems to have a significant positive impact on FDI individually, as well as in the combined form. We also witnessed significant and positive complementarities with each of the institutional factors and productivity, in Issues in Economics and Business ISSN 2377-2301 2020, Vol. 6, No. 2 http://ieb.macrothink.org 2 explaining FDI. This indicated that higher productivity is not the deciding factor of FDI, however, the same productivity in a better institutional environment would produce positive complementarity that would significantly determine FDI. The findings imply that investors' prime concern is not productivity but the institutional environment. Moreover, only with quality institutions, the conventional wisdom persists.


In this paper, we develop a transpire freight impact test system based on ASTM D6537 standard. Test object is the transportation packaging of the laptop computer in the process of drop impact test. Data acquisition are handled using low-pass filter via Matlab software, which calculated four test indicators that consist of peak acceleration, the filtered acceleration, velocity change and pulse duration. We use several drop ways, which the drop height is 40cm and 70cm, respectively. Experiments show that the test object can protect the product safety when drop height is 70cm, but the box will be broken.


Also known as ferroxidase ceruloplasmin, belongs to the family of inflammation-sensitive proteins, and its main function to transport copper in the blood. Although, in addition to this transport function, at present, there are numerous studies that have attempted to use the determination of serum concentrations as a predictive indicator of cardiovascular risk in patients who are overweight or obese. The results of this study confirm the existence of a significant correlation between serum ceruloplasmin and nutritional status of the subjects, which means that for the population of students assessed, serum levels of this protein are an important predictor the risk of cardiovascular disease.


Objective: To develop a new, rapid and sensitive LC-ESI –MS/MS method for the simultaneous estimation of Dapagliflozin and saxagliptin in human K2EDTA plasma by Liquid –liquid Extraction method (LLE) using deutereated dapagliflozin (DGd2) and saxagliptin (SGd5). Method: Chromatographic separation was carried out on a reverse phase hypersil Gold C 18 (50mmx3.0mm, 5μm) column using mixture of 10 mM Ammonium acetate and methanol (20:80, v/v) at a flow rate of 0.5ml/min in isocratic mode. Quantification was achieved using an electro spray ion interface operating in positive mode, under multiple reaction monitoring (MRM) conditions. Results: The method showed excellent linearity over the concentration range of 50.00-10000.00 pg/mL for both the analytes. The intrabatch and inter batch precision (%CV) was ≤4.5% and Matrix effect (%CV) was1.27%, 1.20% for both the analytes. Conclusion: The simplicity of the method allows for application in laboratories, presents a valuable tool for bioavailability, bioequivalence, pharmacokinetic studies.


The advent of the Internet is among the most significant changes in recent decades and has greatly affected the entire range of human experience. However, it has, in turn, led to the emergence of psychopathological features of addiction linked to its use. Literature on the clinical management of the distress related to Internet use systematically measures up to an evolving nosography, with ambiguous definitions of the phenomenon and a diversity of diagnostic, prognostic, and therapeutic criteria. To date, case studies on ''Internet addiction'' treatment are rather limited, and no standard clinical treatment protocols exist. With regard to pharmacological treatment options, empirical or anecdotal assessments are mostly referred to. The aim of this article was to review current literature on Internet addiction treatment and assess the extent to which specific pharmacological interventions alleviate these patients' symptomatic burden, to propose a rationale that may guide the therapeutic approach. To this end, we also explored pharmacological interventions that target patterns of comorbidity and underlying psychopathological dimensions shared with other behavioral or substance addictions.


Cosmological inflation gives a natural answer for a variety of cosmological questions, including the horizon problem, the flatness problem, and others. However, inflation yields new questions relating to the flatness of the inflaton potential. Recent studies of `little' fields, a special class of pseudo-Goldstone bosons, have shown it is possible to protect the mass of a field while still yielding order-one interactions with other fields. In this paper, we will show that `little inflatons' are natural candidates for the slow-roll field of hybrid inflation models. We consider both supersymmetric and non-supersymmetric models, and give a simple examples based on approximate Abelian symmetries which solve the inflaton flatness problem of supergravity. We also present hybrid models in which components of gauge fields in higher dimensions play the role of the inflaton. Protected by higher-dimensional gauge symmetry, they, too, naturally have large couplings while suppressed mass terms. We summarize the implications of the new WMAP data on such models.